Project Summary Transgender women (TW) are at significant risk for HIV infection or transmission as a result of high levels of sexual risk behavirs and co-occurring substance use. Despite HIV and STI rates greater than those of men who have sex with men, there are currently no CDC-approved best evidence interventions to reduce HIV risk for TW. This project seeks to evaluate the efficacy of a peer-led innovative and scalable 7-session hybrid individual- and group-based HIV risk reduction intervention, based on Motivational Interviewing (MI) and Cognitive-Behavioral Skills Training (CBST) with TW in New York City (NYC). The intervention is based on promising findings from a CDC-funded pilot peer-led group intervention for TW, which was shown to be feasible, acceptable, and indicated preliminary efficacy in a short-term follow-up of a non-randomized design with no control group. We propose to expand and refine this intervention, in conjunction with TW and community partners who provide medical, social, and other services for TW, in order to evaluate the longer- term efficacy of a scalable 7-session intervention (two MI-based individual sessions, four MI and CBST-based group sessions, and one MI-based individually-tailored health navigation session) all delivered by TW peer- health navigators (PHN) to reduce risky sex and substance use among TW in NYC. The last session in both conditions will be followed by a phone call from the PHN regarding follow-through with accessing services and facilitation of any needed assistance, and a brief post-intervention assessment of primary outcomes. This randomized control trial (RCT) will examine short (immediate, and 4-months post-intervention) and longer-term (8 and 12-months post-intervention) outcomes between TW randomized to the intervention or an attention control education condition, both of which will include a booster session at 4-months post-intervention. Primary outcomes will be: (1) reductions in sexual risk (self-report and STI incidence), and (2) reductions in substance use (self-report, urine, and substance use related problems) and non-medically monitored hormone treatment and silicone injections. Secondary outcomes will be: (1) increases in resilience (e.g., engagement in care, self- esteem, positive coping), and (2) reductions in minority stress (e.g., internalized transphobia, stigma). In Phase I we will train four TW to be peer health navigators (PHNs) to deliver the 7-session intervention. We will also refine the intervention and develop a 7-session attention education condition based on feedback from PHNs and our community partners. In Phase II, we will recruit 20 TW to pilot both conditions. Participant and PHN feedback will be collected to fine-tune the intervention. In Phase III, 240 TW will be randomized to one of the two arms and outcomes will be assessed over 12-months post intervention. We will conduct biological testing (HIV, Chlamydia, gonorrhea, and syphilis) and collect self-report data to evaluate intervention efficacy. The proposed project will iteratively strengthen an existing promising intervention to provide much needed evidence-based support to reduce the syndemic of risk factors faced by TW, and test the efficacy of a 7- session intervention led by TW peers. This study will be the first in NYC and the US to formally evaluate the utility of a peer-delivered MI and CBST- based intervention tailored for TW, which can then be scalable and replicated in various communities to provide continuous support and protection for this underserved and marginalized vulnerable group.